Sunitinb is chemically described as N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene) methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide as represented by Formula I.

Sunitinb (marketed as Sutent by Pfizer) is an oral multi kinase inhibitor and is useful for the treatment of gastrointestinal tumor and advanced renal cell carcinoma. Sunitinb is commercially available as L-malate salt, described as N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene) methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, (S)-2-hydroxy butanedioic acid (1:1)
Sunitinb and its malate salt are described in corresponding product patent U.S. Pat. No. 6,573,293 (“the '293 patent”), assigned to Sugen and Pharmacia & Upjohn, wherein particular the '293 patent discloses the preparation of sunitinib by the condensation of 5-formyl-2,4-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl) amide with 5-fluoro 2-oxindole in ethanol in presence of pyrrolidine. The reaction sequence is schematically represented as follows:

US2009/0247767 (“the '767 publication”) discloses the preparation of sunitinib by activation of 5-((Z)-(5-fluoro-2-oxoindolin-3-ylidene) methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid to corresponding acid chloride or a carbonyl dimidazole derivative followed by reaction with 2-diethylaminoethylamine. The reaction sequence is schematically represented as follows:

The '293 patent discloses salts of sunitinib, such as positively charged moieties including quaternary ammonium, salts such as the hydrochloride, sulfate, carbonate, lactate, tartarate, malate, maleate, succinate; and negatively charged species; however the '293 patent is silent about the preparation and the nature of specific crystal forms of salts.
U.S. Pat. No. 7,435,832 (“the '832 patent”) discloses free base and salts of sunitinib (e.g. cyclamic acid, maleic acid, hydrobromic acid, mandelic acid, tartaric acid, fumaric acid, ascorbic acid, phosphoric acid, hydrochloric acid, p-toluenesulfonic acid, citric acid, and malic acid salts) had been screened for properties related to the processing of the salt and the preparation of oral pharmaceutical compositions therefrom, including, for example, crystallinity, toxicity, hygroscopicity, stability, and morphology, but only malate salt was chosen from the screening and only two crystal forms of sunitinib L-malate were specifically disclosed.
PCT publication No. WO 2010/011834 discloses acetate salt of sunitinib and polymorphs thereof.
PCT publication No. WO 2010/041134 discloses the preparation of sunitinib malate through generating a weak acid salt where a weak acid is an acid weaker than malic acid. The weaker acid is preferably described is acetic acid.
PCT publication No. WO 2010/049449 discloses D-tartarate, L-tartarate and citrate salts of sunitinib along with their preparation and corresponding polymorphic forms.
PCT publication No. WO 2011/033472 discloses salt of sunitinib with an achiral acid, wherein achiral acid is selected from the group citric acid, p-toluenesulfonic acid, sulfuric acid, acetic acid and methanesulfonic acid.
PCT Publication No. WO2011/100325 discloses salts of sunitinib and polymorphs thereof such as sunitinib fumarate and sunitinib hydrochloride.
PCT Publication No. WO2012/059941 discloses protic acid salts of sunitinib, wherein the protic acid described is hydrochloride, hydrobromide, phosphate or salicylate.
Salts often improve physical and biological characteristics of without modifying primary pharmacological activity, based on mechanism of action. Thus there is a continuing need to obtain new salts of sunitinib having improved physical or chemical properties.
The present invention satisfies this need by providing new salts of sunitinib with a markedly enhanced solubility in water or aqueous media as an essential property of active pharmaceutical ingredients. The new salt forms or the corresponding polymorphic forms of pharmaceutical product can provide the desirable properties such as handling, increased solubility, increased dissolution, decreased hygroscopicity, stability, storage, shelf life and /or ease to purify.
Since sunitinib constitutes an important therapeutic agent, additional and improved ways for preparing sunitinib and its salts is a great value to pharmaceutical science. Thus there is a need in the development of a consistent and novel and (or) an improved process for preparing sunitinib and its salts which is commercially viable , safer for handing, less time consuming and of greater purity.
The reported methods, involving thionyl chloride associated with certain disadvantages, thionyl chloride is a highly reactive substance, which releases hazardous toxic gases such as sulfur dioxide, sulfur chloride or hydrogen chloride. Moreover the reagent found not to be eco friendly. The other reported process involving the use of carbonyl diimidazole found to be disadvantageous being hygroscopic in nature, which requires highly anhydrous conditions. Thus it provides a scope of an improvement in the process for preparation of sunitinib for industrial scale. In order to overcome the problems associated with the reported procedures, inventors thus designed an improved process for the preparation of sunitinib, suitable for industrial scale with better results in the yield.